The invention concerns a method for the production of continuous polymeric solid phase supporting materials for simultaneous combinatory synthesis of organic compounds by means of SPOT synthesis technology, comprised of a polyolefin supporting matrix and individual chains of a graft copolymer, which are synthesized by heterogeneous photoinitiated graft copolymerization of acrylate, vinyl and allyl monomers on the entire surface of the supporting polymer and contain reactive hydroxyl, carboxyl, amino, mercapto, aldehyde or halogen groups, which can be utilized for additional derivatizing.
The chemical synthesis of compounds with the use of the concept of combinatory libraries has an important influence on the process of developing potential candidates for new therapeutic and diagnostic agents. Combinatory chemistry is a technique in which a large number of structurally different compounds are produced under comparable reaction conditions in a cost-favorable and time-efficient manner and can be subsequently introduced into biological testing by high-performance screening assays. The further development of Merrifield""s solid phase synthesis strategy [Merrifield, R. B.: J. Am. Chem. Soc. 1963, 85, 2149], originally introduced for the synthesis of peptides, occupies a key position here. Since the use of excess reagents makes possible nearly complete reactions, and since the methodology can be easily automated and biological test systems can be applied directly onto polymeric surfaces, combinatory chemistry is preferably conducted in the solid phase.
The modification and further development of the original polystyrene supporting systems and the later-used polyamide systems [Atherton, E.; Clive, D. L. J.; Sheppard, R. C.; J. Am. Chem. Soc. 1975, 97, 6584] led to new polymers, such as, e.g., Tentagel and PEGA resins [Rapp, W.; Zhang, L.; Hxc3xa4bich, R.; Bayer, E. In Peptides 1988, (G. Jung and E. Bayer, Eds.) Walter de Gruyter, Berlin, New York, p.199; Meldal, M.; Tetrahedron Lett. 1992, 33, 3077]. These systems were increasingly utilized also for solid phase syntheses of non-peptide substances. Although spherical resin beads of various materials are broadly used, other physical forms such as small rods (polyethylene) or continuous surfaces (cellulose, cotton, glass, polyolefins) have led to new synthesis techniques.
The method of Spatially Addressable Combinatorial Libraries [Review: Pirrung, M. C.; Chem. Rev. 1997,97,473] is such a synthesis concept. A decisive advantage of these substance libraries consists of the fact that the position at which a synthesized molecule is found on the polymer describes its composition. Thus, with the use of supporting materials that are suitable in format and structure, the application of compatible biological test systems can lead directly to information relative to the biological activity of the synthesized substances.
The form of appearance, the chemical and physical properties and the surface functionalization of the supporting materials thus act decisively on both the quality and efficiency of the synthesis as well as on compatibility with biological test systems.
The SPOT technology developed by Frank [Frank, R.; Tetrahedron, 1992, 48, 9217] for constructing peptides on planar cellulose surfaces makes particularly possible the efficient parallel construction of large numbers of peptide sequences. The method in which the reagents are pipetted to local addresses on the continuous support is further characterized by applicability of conventional screening assays, since the readout geometries of high-performance test systems are compatible with the planar supporting materials. Thus, for example, SPOT arrays could be utilized, in addition to classical epitope mapping, in order to discover optimal binding sequences of protein kinases or metal-binding peptides [Tegge, W.; Frank, R.; Hoffman, F., Dostmann, W. R. G.: Biochemistry 1995, 34,10569; Malin R.; Steinbrecher, R., Jannsen, J.; Semmler, W.; Noll, B.; Johannsen B.; Frxc3x6mmel, C.; Hxc3x6hne, W.; Schenider-Mergener, J.: J. Am. Chem. Soc. 1995, 117,11821].
Based on the limited chemical and mechanical stability of the cellulose membranes, however, the technology has been previously limited, to the production of peptide sequences that are produced under relatively mild synthesis conditions.
Due to the structure of the chemically homogeneous support and the utilization of hydroxy groups as reactive groups, the permanent excess of hydroxy functions on the cellulose surface leads to the fact that selective or complete reactions cannot be achieved. This is a particular disadvantage for the generation of different linker constructs, which decisively limits the variety of possible reactions.
Several developments in the field of planar supporting materials could overcome the disadvantages of cellulose under certain conditions for SPOT synthesis, but have previously not been applied to the SPOT synthesis technique.
Thus, the patents of Berg et al. (WO 90/02749, WO 91/13098) and Batsberg et al. (WO 95/00533) describe the use of polyolefin films (preferably polyethylene). These were modified by gamma irradiation or by means of chemically initiated graft polymerization and homopolymerization of styrene from alcoholic solutions. Another chemical derivatization for introducing reactive groups followed. The supports produced in this way were used in reactors for peptide and oligonucleotide synthesis. In addition, solid-phase assay (ELISA) could be conducted.
Although the grafting of polystyrene chains is a logical further development of the classic Merrifield resin for a planar support, while maintaining conventional peptide synthesis conditions, the selection of this polymer in this context is not compelling. In contrast, it even introduces disadvantages, such as, e.g., the greatly different salvation of the chains in different solvents. In addition, polyethylene is less mechanically stable than the preferred base polymer and the described films or other molded bodies that have been are generally not porous. Possible functionalizing is thus limited to the external surface (i.e., thick or thin grafted layer), which leads to a smaller charge capacity. A surface-selective functionalization is not assured. In fact, additional reactions (e.g., graft polymerization and homopolymerization) are triggered in the polyolefin film by the selection of xcex3-irradiation for initiating, particularly in the monomer/solvent system, but these reactions only reinforce the mechanical instability and cause a turbidity, which prevents application in assays.
Further, polypropylene membranes also functionalized with amino groups were described by Hudson et al. (WO 94/05394) in addition to the use of porous sintered plates, and a hydrophilic polymer (dextran, partially hydrolyzed chitin) is covalently coupled to these membranes by means of a spacer (PEG). The hydrophilic support materials used in small reactors (grid plates with holes) possess a uniform reactivity and are well suitable for screening purposes. Of course, the harsh primary modification via chromium oxidation is a particular disadvantage with respect to the use of porous supporting materials (with large specific surface and thus more sensitive morphology). Thus the membranes obviously can be handled only when they are fixed in the grid plates, i.e., as discontinuous supporting materials. In addition, the relatively expensive construction of the synthesis device leads to a strictly limited capacity and limited variability of the individual synthesis areas.
The patent of Koster et al. (EP 0 305,929) describes the synthesis of peptides and oligonucleotides on porous membrane polymers, on which reactive groups were produced on the surface by irradiation-initiated generation of radicals. The functionalization by means of very different (due to the selection of initiator and monomers) and strongly crosslinked polymer layers, however, may lead to nonuniform accessibility of the functional groups. Thus, these membranes appear unsuitable for SPOT synthesis. The suitability of large surfaces for synthesis and bioassays (which require stability and the same accessibility of all reactive groups) cannot be found here. In general, complications are to be expected in the case of solid phase synthesis of longer and/or more complex sequences.
Coassin et al. (WO 95/09176) reported on a polymer functionalization (polypropylene) with suitable reactive plasma (e.g., ammonia) in order to arrive at films and membranes as supports for the synthesis and sequencing of biomolecules. The functionalization, however, is accompanied by secondary reactions (oxidation), which clearly adversely affect the mechanical stability of the support. In addition, plasma functionalization, as is known, is not very chemoselective. The result is a small charge with reactive groups, since the modification is produced only on the surface and the flows of charge carriers and reactive species (in the case of reactive plasmas) must be minimized due to the degradation effect (see above).
Large-surface continuous supporting materials were described also by Eichler (DD 272,855 A1), Lebl et al. (EP 0 385,433 A2; EP 0 445,915 A1) and Okrongly et al. (EP 0 400,920). Whereas the first two patents refer to the modification of cellulose with the known disadvantages, in the latter, microtiter plates (polystyrene) are preferably functionalized on the surface for peptide synthesis. An advantageous monitoring of the course of reaction by means of UV spectroscopy, however, here contrasts with the disadvantages of a limited binding capacity as well as a limited mobility of the target molecules, each time due to the limitation of the functionalization to a simple polymer-like reaction at the non-porous polystyrene surface.
All of the systems of the prior art (functional supporting materials and synthesis conditions) have special serious disadvantages from the viewpoint of the requirements of SPOT synthesis, which prevent an effective application. In particular, a widespread application of SPOT synthesis for generating organic chemical substance libraries is impossible with the known continuous solid phase supporting materials. These disadvantages or limitations are overcome with the invention, which is described below.
The object is solved by a method for the synthesis of continuous polymeric solid phase supporting materials with spatially defined reaction sites that are separated from one another, comprising a supporting matrix and graft copolymer chains with reactive groups, which can react with organic compounds, with the following synthesis steps:
i.) Coating of the surface of the supporting matrix with a photoinitiator, which generates radicals at the polymer surface after UV excitation, by extraction of hydrogen and thus essentially without polymer degradation in the matrix,
whereby the supporting matrix belongs to the group of at least one of the polymeric polyolefinic base polymers: polypropylene, polyethylene, polyvinylidene fluoride, polytetrafluoroethylene or crosslinked polystyrene, preferably polypropylene
whereby the photoinitiator is a benzophenone derivative or ketone.
ii.) Exposure of the supporting matrix coated with photoinitiator with UV irradiation in the presence of an unsaturated functional monomer
whereby the functional monomer contains a spacer group, which is covalently bound via an amide, ester, ether, disulfide or CC group with both a reactive group as well as also with a group capable of polymerization.
(xcex1) the spacer is an oligo or polyethylene glycol or a bond,
(xcex2) the polymerizable group is an acrylate, vinyl or allyl monomer,
(xcex3) the reactive group, which can react with organic compounds, is a hydroxyl group, carboxyl group, amino group, mercapto group or a halogen group,
(xcex4) if necessary, a bond between the reactive group and the spacer or between the spacer and polymerizable group can be cleaved hydrolytically or by oxidation/reduction.
iii.) Formation of graft copolymer chains by covalent bonding of the polymerizable group of the functional monomer to the supporting matrix, whereby a monomer is first added to a radical of the polymeric supporting matrix and then other monomers are added to this [first] monomer in the sense of a polymerization.
iv.) Extraction of unreacted functional monomer and photoinitiator as well as of soluble secondary products.
The subject of the present invention is a method for the production of a new type of polymeric surface, on which organic substance libraries can be produced with the use of the SPOT synthesis concept, and their biological activity can be evaluated and read out directly on the supporting material.
According to the invention, surface-functionalized solid phase supporting materials are synthesized, which overcome the disadvantageous properties of current supporting materials indicated above in the description of the prior art or make possible completely alternative synthesis designs and techniques of combinatory synthesis by new functionalization strategies.
The good mechanical properties (stability) of the supporting material and a well-defined surface functionality are equally essential for the special requirements of SPOT synthesis. Of course, there are no homogeneous materials, which a priori combine these two properties. The example of chemically homogeneous cellulose, wherein new potential hydroxyl reactive groups continually are formed from the carbohydrate matrix upon application as a solid-state, hydroxyl-reactive supporting material, teaches rather that an optimal supporting material should be chemically heterogeneous. A supporting matrix, which essentially provides stability, with a chemically heterogeneous functional surface [is required].
Consequently, the heterogeneous functionalization of suitable polymetric matrix materials represents the most attractive synthesis path for obtaining new, continuous polymeric solid phase supporting materials that provide better performance. If this functionalization can also successfully lead to a surface selectivity, i.e., the chemical conversion of the matrix polymer can be limited to its surface, then supporting matrix and functional supporting surface can be optimized independently of one another.
The requirements for the supporting matrix result from the fact that a good, reliable manipulation before, during and after the multistep syntheses is a decisive factor for the success and quality of the syntheses and assays. On the other hand, a large specific surface in combination with suitable pore structure of the supporting matrix is the prerequisite for a high binding capacity per unit of surface. A sufficient dimensional stability (minimum swelling), however, must also be present, in order to be able to obtain a repositioning of the membrane during the syntheses and to obtain defined products in each spot and to read out the assay results without falsification. All of these requirements make it necessary that the supporting matrix must have an excellent mechanical, thermal and solvent stability under synthesis and assay conditionsxe2x80x94despite the desired large specific surface.
The requirements for the functional surface with respect to synthesis are that the reactive groups be present in large quantity (at least up to 1 xcexcmole/cm2) and with good, constant accessibility (over all synthesis steps for the target molecules). This requires a large specific surface in combination with suitable pore structure of the supporting matarix (see above) as well as reactive groups at spacer groups or spacer chains, a good salvation of the functional groups and an optimal wetting of the external supporting surface (defined spots with minimal radial concentration gradients; no chromatography effects). In this way, a high product purity (per spot) and identical product quantities are obtained for all spots.
With respect to the assays, in addition, the accessibility and mobility of the synthesized molecules as well as minimal nonspecific interactions of the functional surface with the test proteins (minimum background for the readout of the results) are essential.
The production method will be robust, reproducible and flexible with respect to functionality and also the supporting matrix, as the case may be, as well as make possible a problem-free scaling-up to large surfaces. The new continuous polymeric solid phase supporting material, particularly the homogeneity and the stability of the supporting matrix, functional layer and its composite under synthesis and assay conditions are critical for the synthesis product.
Synthesis of the New Continuous Polymeric Solid Phase Supporting Materials
A polymer that is particularly well suitable as the supporting matrix is polypropylene, since it can be mechanically loaded and is chemically stable over broad regions of potential organic chemistry synthesis conditions (including a wide range of solvent and temperature conditions). A swelling barely occurs, except with very apolar solvents, which, however, play no role in synthesis. Polypropylene is available both in the form of thin, homogeneous, transparent films, as well as thick foils or plates, but also as a porous membrane with different pore morphologies and sizes. Depending on the target application (capacity desiredxe2x80x94specific surface; mechanical flexibility), base materials for the synthesis of solid phase supporting materials can be selected from this spectrum. Preferably, macroporous flat membranes of polypropylene are selected as the supporting matrix (e.g., microfiltration membranes, produced by phase inversion and with sponge-like pore network with nominal pore size/mesh of 0.2 xcexcm or filters with a spun and sintered nonwoven network structure with nominal pore size/mesh of 0.6 xcexcm). Of course, other polymers, such as, e.g., polyethylene, polyvinylidene fluoride, crosslinked polystyrene or teflon with different morphologies may also be used. The supporting matrix may also be reinforced externally or internally by an additional inert supporting material or particles, fibers or networks of polymer, glass or metal.
In order to assure maximum stability under application conditions, a composite of the supporting matrix and a functional layer chemically anchored thereon is synthesized. The supporting matrix is preferably covalently functionalized by photoinitiated heterogeneous graft copolymerization with long graft polymer chains of functional monomers (strongly surface-selective with respect to the polypropylene matrix, but nearly uniform over the entire layer thickness). The new continuous polymeric solid phase supporting materials according to the invention for SPOT synthesis are obtained according to a method, which is comprised of the following essential steps:
i) Surface coating of the supporting matrix with a photoinitiator, which can generate radicals at the supporting surface after UV excitation (by hydrogen abstraction and thus without degradation of the matrix polymer);
ii) UV exposure of the coated supporting matrix in the presence of a functional monomer or monomer mixture with the formation of a functional layer, which consists of non-crosslinked functional graft copolymer chains anchored covalently to the matrix polymer (the UV exposure is preferably produced selectively, so that only the photoinitiator is excited);
iii) Extraction of unreacted monomers and photoinitiators as well as of soluble homopolymers or copolymers or photoinitator byproducts.
FIG. 1 shows schematically the production method for continuous planar solid phase supporting materials.
A sequential activation/initiation of graft copolymerization is also possible by first exposing the supporting matrix coated with photoinitiator according to i) in the presence of oxygen or with subsequent exposure in oxygen with the formation of supporting polymer peroxides and then the reaction with the monomer is thermally initiated. Other heterogeneous chemically initiated reactions may also be applied for initiating a graft copolymerization.
Benzophenone and structuraly related ketone derivatives are particularly suitable as the photoinitator. Coating with a photoinitator in step i) may be conducted by dip-coating or impregnating from a solution in a solvent that does not dissolve the supporting polymer; however, it may also be produced directly prior to the graft copolymerization described in step ii) without additional process step, by adsorbing the photoinitator from a mixture of initiator, monomer or monomer mixture and, if necessary, solvent, on the supporting-material surface.
A structural constitution that can lead to a multiple number of surface functionalities in a modular manner according to a uniform reaction mechanism (heterogeneous graft copolymerization) is common to the monomers used:
Reactive group-spacer group-polymerizable group
Functional acrylates, methacrylates, acrylamides or methacrylamides are preferably used, but also other functional vinyl monomers and many others are suitable, in principle. Examples of reactive groups as an anchor for solid phase synthesis are hydroxyl or amino groups. Carboxyl or epoxy groups introduced by functional monomers may also be very easily used for this purpose (e.g., after xe2x80x9crefunctionalizingxe2x80x9d to amino groups). Oligo or polyethylene glycol chains are particularly suitable as spacer groups, since they can be well solvated in a similar way in many different solvents, guarantee a good mobility, and also improve biocompatibility. Cleavable linker structures may be, e.g., esters (in acrylates) or amides (in acrylamides), wherein the latter have an essentially better stability against hydrolysis and are preferred for solid phase syntheses under harsh organic chemical conditions. Hydroxy or amino (polyethylene glycol) methacrylates or methacrylamides are examples of monomers, that can be graft copolymerized to yield, supporting materials, which can be used directly with special advantages for SPOT synthesis. Supporting materials functionalized with graft polyacrylic acid can simply be xe2x80x9crefunctionalizedxe2x80x9d with diamino-oligoethylene glycols to form hydrolysis-stable amino supporting materials.
The above-named functional monomers can be utilized in mixture with other functional monomers, and also with inert monomers, for the preparation of graft chains of copolymers. The latter inert monomers may be utilized for xe2x80x9cdilutionxe2x80x9d of reactive groups at/in the solid phase supporting material or for adjusting the hydrophilic or hydrophobic nature or adjusting the charge (which is essential under certain circumstances for assay compatibility).
In the above-given supporting matrix, with corresponding homogeneous or porous structure and thus a smaller or larger specific surface, the degree of functionalization and thus the loading with reactive groups per unit of surface can be adjusted within a wide range (up to 10 xcexcmoles/cm2) by the graft copolymerization conditions (photoinitiator coating, monomer concentration, exposure time). An increase in capacity is achieved by the graft copolymer chains in any case, compared with a polymer-like functionalized flat support surface. By selecting suitable conditions (light absorption of photoinitator and supporting matrix), uniform functionalizations of thick porous layers (with BP [benzophenone] in the case of PP [polypropylene] membranes up to 200 xcexcm) are possible.
The preferably applied photofunctionalization permits, by a rapid and effective process, the reproducible and uniform functionalization of large continuous solid phase supporting material surfaces.
Syntheses on the New Continuous Polymeric Solid Phase Supporting Materials
By the selected production method, it is possible to generate primary reactive groups, preferably amino or hydroxyl groups, in large number ( greater than 1 xcexcmole/cm2) with good accessibility on a solid supporting matrix. Interestingly, this accessibility remains nearly constant even over a large number of synthesis cycles (10% decrease in load after approximately 10 synthesis cycles). The reason for this is the large specific surface in combination with the suitable pore structure of the supporting matrix of the supporting material (porous membrane) as well as a very good mobility of the reactive groups, caused by solvated graft copolymer chains and additional spacer groups. In addition, optimal wetting of the external support surface leads to defined spots with minimal deep-bed filtration effects and radial concentration gradients. Due to the constant excess of reagent caused thereby at each site of the wetting, a nearly constant product quality can be assured. Based on the homogeneity of the solid phase supporting material (identical number of equally accessible functionalities over the entire surface), identical quantities of product can be generated per spot. In addition, the reduced hydrophobia of the modified solid phase supporting material, in comparison to the supporting matrix, and in combination with the mobility of the bound substance induced by the spacer structures, leads to a good assay compatibility.
The polymeric solid phase supporting materials are further characterized by high chemical stability, i.e., resistance to strong acids, lyes, solvents as well as oxidizing and reducing reagents. In addition, the new polymeric solid phase supporting materials possess a high stability against physical influences such as temperature, ultrasound and microwave treatment, which results in the fact that the continuous surfaces show no swelling or only negligible swelling even after several reaction cycles. These properties permit a repeated, locally addressed pipetting of minimal volumes (10 nl) and in contrast to cellulose, an extensive variation of chemical reaction conditions.
The new continuous polymeric solid phase supporting materials can be prepared with a multiple number of linker constructs for taking up other molecules. Thus, in addition to acid-sensitive linkers (e.g., Rink linkers), UV-activatable photolinkers (e.g., 4-(methoxy-4-(2-Fmoc-aminoethyl)-5-nitrophenoxybutyric acid), base-labile linkers (e.g., HMBA linkers) or linker constructs that can be cleaved with aqueous buffer systems (e.g., imidazole linkers) can be used. These linkers can also be applied in parallel on the continuous solid phase supporting material by locally defined application of spots and can be utilized, e.g., for the synthesis of multiply or gradually cleavable products.
Although peptide substances of the same or better quality than in the case of conventionally used celluloses can be produced, in particular, a number of other possibilities result from the above-named properties of the new solid phase supporting materials for the synthesis of substance libraries produced by organic combinatory techniques. Since the new solid phase supporting materials according to the invention possess a high chemical and physical stability, their decisive advantages lie particularly in the combinatory synthesis of libraries of unnatural oligomers (e.g., peptoids, oligocarbamates, oligoureas, azatides, ketides, peptide sulfanamides, vinylogenic sulfonyl peptides) as well as small synthetic molecules (e.g., benzodiazepines, triazines, triazoles, hydantoins, cubans, xanthines, pyrrolidines, xcex2-lactams, thiazolidones). Further, a key application lies in the parallel synthesis of chimeras (conjugates) of different synthetic (natural or unnatural) oligomers or small synthetic molecules with natural materials, such as, e.g., steroids or sugar molecules.
The use of continuous solid phase supporting materials, which have been produced according to the method of the invention is advantageous for the parallel and combinatory synthesis of support-bound or free compounds, which are synthesized by SPOT synthesis of activated synthesis building blocks at different reaction sites on the continuous solid phase supporting material.
A use according to the invention of the continuous solid phase supporting materials for the parallel and combinatory synthesis of proteins is preferred.
More preferred is a use according to the invention of the continuous solid phase supporting materials for solid phase synthesis, preferably SPOT synthesis, both as an array of identically or differently functionalized supporting materials or as a stack of identically or differently functionalized supporting materials for the synthesis of multiply or gradually cleavable compounds, whereby a quasi-three-dimensional combinatory technique is possible by split (single sheets) and combine (stack) techniques with whole supports.
Still more preferred is the use according to the invention of the continuous solid phase supporting materials for the identification of molecules (ligands) of synthesized compounds, comprising the following steps:
Incubation with the ligand, removal of excess ligand by washing, detection of bound ligands by suitable methods such as: i) immunological detection, ii) detection of bound radioactively-labeled ligands, iii) fluorescence or chemoluminescence detection, iv) biosensory detection.
Most preferred is the use according to the invention of the continuous solid phase supporting materials for supporting enzymatic activities of synthesized compounds, comprising the following steps:
i.) Incubation with the enzyme,
ii.) detection of enzymatic activity.
The invention will be described in more detail in the following based on examples, which explain the synthesis of the new continuous polymeric solid phase supporting materials, their application in SPOT synthesis of peptides and other organic chemistry molecules as well as of substance libraries comprised of peptides and other organic chemistry molecules, and application in analytical and screening systems. Of course, the invention is not limited to these concrete examples.
Solid Phase Synthesis
Covalent coupling of molecules with an insoluble polymeric supporting material and subsequent reactions of the support-bound substances, whereby excessive reagents can be used and then separated by simple washing and filtering operations, and the target product remains bound to the polymeric supporting material until it is cleaved.
Functional Monomers
Molecules, which contain a polymerizable group, a spacer group and a reactive group and can form linear and/or branched polymer chains under the influence of a polymerization initiator.
Continuous Solid Phase Supporting Material
Planar material comprised of a supporting matrix (see below) with graft copolymer chains (see below) covalently anchored thereon.
Ligand
Molecule, which binds to the compound synthesized on the continuous solid phase supporting material and/or reacts with it chemically, and which can be a protein, enzyme, carbohydrate or glycoprotein, lipid or lipoprotein, a nucleic acid or a low-molecular compound.
Linker
Molecularly cleavable anchor molecule, which permits the cleavage of the synthesized target products from the solid phase supporting material
Graft Copolymer Chains
Linear and/or Branched Molecule Chains, Constructed from Functional Monomers (see below)
Photoinitiator
Produces radicals, which can react with a functional monomer, e.g., a benzophenone derivative or ketone, after coating the surface of a supporting polymer and excitation by means of UV irradiation by hydrogen abstraction from the supporting polymer.
Polymerizable Group
Reaction-capable multiple bond in functional monomers, e.g., an acrylate, vinyl or allyl group.
Radicals
Electrically neutral molecules, which possess a magnetic moment; a preferred reactivity is the addition to compounds, which contain reactive multiple bonds (polymerizable groups).
Reactive groups
Reactive chemical group (functionality) for covalent coupling reactions with other compounds, e.g., a hydroxyl group, carboxyl group, amino group, mercapto group or a halogen group.
Spacer Group
Molecular spacer between polymerizable group and reactive group in a functional molecule, e.g., an oligo or polyethylene glycol or a bond.
Spot
Is formed by the pipetting of reagents onto coherent continuous surfaces, whereby the pipetted volume defines the size of the SPOT and the number of possible SPOTs per unit of surface.
Spotting
Pipetting of Reagents onto Coherent Continuous Surfaces
SPOT synthesis
Solid phase synthesis concept in which SPOTs will be defined by pipetting of small drops of reagent onto a predefined array of reaction sites on a coherent continuous solid phase supporting material, which functions as the polymeric solid phase supporting material; these SPOTs represent microreactors, in which solid phase syntheses can occur, if solvents with low vapor pressure are used.
Supporting Matrix
Chemically and morphologically stable, planar material, which is comprised of polyolefin polymers (supporting polymers) such as polyethylene, polystyrene, polyvinylidene fluoride, polytetrafluoroethylene, but preferably polypropylene.
UV Excitation
Converts the photoinitiator into an Excited State without Exciting (Degrading) the Supporting Polymer